Day 1 :
National Institute of Neurological Disorders and Stroke – NIH, USA
Keynote: Aberrantally activated Cdk5 as a target for therapeutic approaches to neurodegenerative disorders like Parkinsion’s and Alzheimer’s Diseases
Time : 09:30-10:10
Pant received his M.A. and Ph.D. degrees in Physics from Agra University, Agra, India. His postdoctoral studies were conducted on the mechanisms of electron and ion transport in model membrane systems at the Department of Biophysics at Michigan State University. He joined the Laboratory of Neurobiology in the NIMH as a senior staff fellow in 1974 with Dr. Ichiji Tasaki where he studied the function of the axonal cytoskeleton in the squid giant axon. In 1979 he moved to the NIAAA extending his studies on the neuronal cytoskeleton and the effects of alcohol on its regulation. Pant moved to the NINDS, Laboratory of Neurochemistry in 1987 where he is presently chief of the section on Cytoskeleton Regulation. His laboratory is studying the mechanisms of topographic regulation of neuronal cytoskeleton proteins by post-translational modification, including the role of kinase cascades in normal brain and during neurodegeneration.
Our previous studies have shown that neuro-filaments & Tau the major neuronal cytoskeletal proteins are selectively phosphorylated in axons.The phosphorylation activity is tightly regulated under physiological conditions. Under neuropathological conditions, however, phosphorylation is deregulated, occurs abnormally in perikarya and induces pathology resembling that seen in many neurodegenerative diseases e.g. AD, ALS, PD). We identified cyclin dependent kinase 5 (Cdk5) together with its activator p35, as a major kinase regulating the topographic neuronal cytoskeleton phosphorylation.It is found that Cdk5, when deregulated by neuronal insults (A-beta, glutamate, oxidative stress, mutations and other), is hyper-activated as a stable complex with p25 (a truncated fragment of p35) and induces perikaryal hyper-phosphorylated tau, synuclein and NFPs as seen in AD, PD and ALS. At autopsy, AD, PD and ALS brain display hyperactive Cdk5 (Cdk5/p25) and have confirmed that Cdk5/p25 induces neuro-inflammation, tau and NF hyperphorylation along with cell death. A p25-overexpressing (P25Tg) AD model mouse displays the typical AD phenotypes. Accordingly, hyperactive Cdk5/p25 has been identified as a possible therapeutic target for neurodegeneration. All the therapeutic approaches inhibiting activities of kinases have been by interfering with ATP binding domains of the kinases that turned out to be non-specific and highly toxic. To modulate the Cdk5 activity instead of using the analogs of ATP we decided to study the effect of different truncated fragments of p35 on the regulation of Cdk5 activity. We identified a 126 amino acid (aa) truncated peptide of p35, (CIP) and smaller peptide p5 (24 aa) bind with Cdk5 with higher affinity than p25 and selectively inhibited Cdk5/p25 hyperactivity in culture, reduced tau, NFP hyper-phosphorylation and cell death without toxicity and affecting endogenous Cdk5/p35 activity. The question arose; will CIP and p5 be non toxic in vivo, in animals as in cell cultures and may prevent the phenotypes of an AD, PD and ALS transgenic mice models? Consistent with the model, we succeeded in showing that pathological and behavioral phenotypes in AD, PD and ALS model mice (over-expressing p25 transgenic) and the 5XFAD double transgenic can be alleviated after co-expression with CIP in p25 Tg and treatment with modified p5 (TFP5). We propose that CIP and TFP5 is novel therapeutic candidate to prevent Alzheimer’s disease phenotypes and pathologies.
Geneva University School of Medicine, Switzerland
Panteleimon Giannakopoulos obtained his MD degree in the University of Athens in 1989 before completing a full training on psychiatry and psychotherapy in
London (Maudsley Hospital and Geneva) as well as postdoc training in Paris (La Pitié-Sâlpetrière Hospital, Federation of Neurology). In 1998, aged 33 years,
he has been appointed as associate professor and medical head of the Division of Geriatric Psychiatry of the University Hospitals of Geneva. Later on (2004) he
obtained the position of full tenured professor of Psychiatry in the University of Geneva. From 2003 to 2011, he also assumed a parallel position of full professor
of Old Age Psychiatry in the University of Lausanne in order to promote the academic careers of junior staff locally. He has been Chairman of the Department of
Mental Health and Psychiatry in Geneva for ten years (2005-2015) and vice dean of the Faculty of Medicine in the University of Geneva in charge of postgraduate
and continuous education (2003-2011). From December 1st 2015, he is the medical head of the forensic psychiatry development in Geneva county. Specialist of
Alzheimer disase research, he published more than 220 peer reviewed articles in the fi eld of neurobiology of aging with particular focus on predictive biomarkers
of cognitive decline.
The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report confl icting
results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of
cognitive decline. Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling
controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral
microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identifi ed cases with subtle
cognitive defi cits were referred to as controls with a deteriorating condition. Group diff erences in radiologic parameters were studied
by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coeffi cients. Cerebral microbleed prevalence was
similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%).
In all diagnostic groups, lobar cerebral microbleeds were more common. Th ey occurred in 20.1% of all cases compared with 6.5% of
cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline
Mini-Mental State Examination score, and the Fazekas score) were signifi cantly associated with cognitive deterioration with the
exception of education of >12 years showing a slight but signifi cant protective eff ect (OR, 0.44; 95% CI, 0.22-0.92; P = .028). Th e
Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep
location of cerebral micro
University of Wisconsin, USA
Keynote: New approach to Neurorehabilitation: Cranial nerve noninvasive neuromodulation (CN-NINM technology)
Time : 10:00-10:40
Yuri P. Danilov, PhD, Senior Scientist and Neuroscience Director in Tactile Communication and Neuromudulation Laboratory (TCNL), Biomedical Engineering Department,
UW-Madison, is a system neuroscientist with over 35 years’ experience in research on brain functions and the special senses, including vision, taste, hearing and balance.
He is the lead discoverer of the balance retention effect, lead development of the specifi c training regimens, and continues to identify potential clinical and non-clinical
application of neuromodulation and sensory substitution technology. He received the M.S. degree in biophysics, in 1978, from St. Petersburg University in Russia and the
Ph.D. degree in neuroscience, in 1984, from the Pavlov Institute of Physiology, USSR Academy of Science. He was Senior Scientist (11/00 – 12/04) and Director of Clinical
Research at Wicab, Inc., where as co-inventor oversaw both conceptual development for the BrainPort vision and balance systems. He is a co-inventor the CN-NINM
technology and his interest areas are neuroplasticity, neurorehabilitation, enhancement of human performance.
Cranial-Nerve Non-Invasive NeuroModulation (CN-NINM) is a primary and complementary multi-targeted rehabilitation
therapy that initiates the recovery of multiple damaged or suppressed brain functions that are aff ected by neurological disorders.
CN-NINM was originally developed in our lab to facilitate and enhance the brain's innate ability to reorganize and “normalize”
its functional activity during targeted physical and occupational therapy, and thus improve movement control and cognition. It is
deployable as a simple, home-based device (portable tongue neurostimulator, PoNSTM) and training regimen following initial patient
training in an outpatient clinic. It may be easily combined with all existing rehabilitation therapies, and may reduce or eliminate need
for more aggressive invasive procedures or decrease the total medication intake.
CN-NINM uses sequenced patterns of electrical stimulation on the tongue. Our hypothesis is that CN-NINM induces
neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII. Th is stimulation excites
a natural fl ow of neural impulses to the brainstem (pons varolli and medulla), and cerebellum via the lingual branch of the cranial
nerve (CN-Vc), and chorda tympani branch of CN-VII, to eff ect changes in the function of these targeted brain structures, extending
to corresponding nuclei of the brainstem – at least in the sensory and spinal nuclei of trigeminal nuclei complex and the caudal part
of the nucleus tractus solitarius. We postulate that the intensive activation of these structures initiates a sequential cascade of changes
in neighboring and/or connected nuclei by direct collateral connections, brainstem interneuron circuitry and/or passive transmission
of biochemical compounds in the intercellular space. Combining neurostimulation with a specifi c set of physical, cognitive and/or
mental exercises we can further focus brain rehabilitation and target our eff ort on recovery of selected functional damage. Th e result is
essentially brain plasticity on demand – a priming or up-regulating of targeted neural structures to develop new functional pathways,
which is the goal of neuro-rehabilitation and a primary means of functional normalization and recovery.
CN-NINM represents a synthesis of a new non-invasive brain stimulation technique with applications in physical medicine,
cognitive, and aff ective neurosciences. Our new stimulation method appears promising for treatment of a full spectrum of movement
disorders, and for both attention and memory dysfunction associated with traumatic brain injury. Th e integrated CN-NINM therapy
proposed here aims to restore function beyond traditionally expected limits by employing both newly-developed therapeutic
mechanisms for progressive physical and cognitive training - while simultaneously applying brain stimulation through a portable
neurostimulation device. Based on our previous research and recent pilot data, we believe a rigorous in-clinic CN-NINM training
program, followed by regular at-home exercises that will also be performed with CN-NINM, will simultaneously enhance, accelerate,
and extend recovery from multiple impairments (e.g. movement, vision, speech, memory, attention, and mood), based on divergent,
but deeply interconnected neurophysiological mechanisms.
- Session on: Brain Disorders | Neurodegeneration and Aging Disorders
Geneva University School of Medicine, Switzerland
University of Twente, The Netherlands
Time : 11:50-12:15
Kerensa Broersen completed her Doctorate in the field of protein aggregation at Wageningen University in The Netherlands in 2005. After her Post-doctoral study at the MRC-LMB in the UK, she joined the Free University of Brussels (VUB)/Flanders Institute for Biotechnology (VIB) in 2007. Here, she headed a research team that studied the molecular mechanism of Alzheimer’s disease. This led to the discovery of molecular pathways of a number of risk factors that affect Alzheimer’s disease pathobiology. Subsequently, she joined the Nanobiophysics Group at the University of Twente/MIRA Institute in The Netherlands as an Assistant Professor investigating further the impact of protein structures on human health with her team
One of the most prominent hallmarks detected in the brain of patients suffering from Alzheimer’s disease is the deposition of amyloidogenic plaques. These plaques are largely composed of the amyloid-beta peptide. It has been demonstrated that, even though these plaques comprise an important and recurring feature for disease, that precursor forms of these plaques, called ‘oligomers’ or ‘protofibrils’ more potently affect neuronal functioning. The amyloid-beta peptide arises from cleavage of trans-membrane amyloid precursor protein through cleavage by means of a combination of secretase enzymes. As a result of this enzymatic processing, genetic profile and further modifications, the amyloid beta peptide does not exist as a well-defined species but arises in a variety of truncated and modified forms. For example, it has been reported that, within any one individual, a range of amyloid beta peptides exist varying in length from 34 to 49 amino acids and that multiple otherwise modified forms of this peptide are present in a complex mixture. We have shown that small shifts in the composition of the amyloid beta pool can have significant impact on the aggregation reaction, cellular response and cognitive behavior in animal models. The mechanism by which hence formed variants of the amyloid-beta peptide cause disease still remains elusive. In aim to determine how amyloid beta peptide manifests its pathological effects, we use Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy, mass spectrometry and immunohistochemistry to monitor peptide aggregation.
Geneva University School of Medicine, Switzerland
Time : 12:15-12:40
P. Giannakopoulos was Born in 1965 in Greece and obtained his MD degree in the University of Athens in 1989 before completing a full training on psychiatry and psychotherapy in London (Maudsley Hospital and Geneva) as well as postdoc training in Paris (La Pitié-Sâlpetrière Hospital, Federation of Neurology). In 1998, aged 33 years, he has been appointed as associate professor and medical head of the Division of Geriatric Psychiatry of the University Hospitals of Geneva. Later on (2004) he obtained the position of full tenured professor of Psychiatry in the University of Geneva. From 2003 to 2011, he also assumed a parallel position of full professor of Old Age Psychiatry in the University of Lausanne in order to promote the academic careers of junior staff locally. He has been Chairman of the Department of Mental Health and Psychiatry in Geneva for ten years (2005-2015) and vice dean of the Faculty of Medicine in the University of Geneva in charge of postgraduate and continuous education (2003-2011). From December 1st 2015, he is the medical head of the forensic psychiatry development in Geneva county. Specialist of Alzheimer disase research, he published more than 220 peer reviewed articles in the field of neurobiology of aging with particular focus on predictive biomarkers of cognitive decline.
Early clinic-pathological studies demonstrated that the two cardinal lesions associated with Alzheimer disease (AD), neurofibrillary tangles (NFT) and amyloid deposits, have a differential impact on cognition both at early and late stages of the neurodegenerative process. In contrast to ß-amyloid (Aß) deposition that occurs diffusely in the human brain over 60 years of age, NFT formation follows hierarchical schemes of regional and cellular vulnerability affecting first the entorhinal cortex and parahippocampal formation before moving in adjacent neocortical association areas. Long before the emergence of novel imaging techniques, it was clear that Aß deposits correlate very weekly with cognition and downstream neurodegenerative biomarkers. In contrast, NFT and associated synaptic loss is strictly related to the loss of cognitive functions not only at late but also at early stages of AD. The last decade was characterized by the exponential increase of knowledge in the field of AD predictive biomarkers and, most importantly, characterization of tracers for ß-amyloid (Aß). It is now widely acknowledged that amyloid deposits in positron emission tomography (PET) with Pittsburg compound B (PiB; a marker of Aß fibrillar deposits) precede dementia by 5-10 years, and PiB burden inversely correlates with concentration of Aβ42 in the cerebro-spinal fluid. However, increased PiB burden was reported in nearly 20% to 30% of controls in the general population pointing to the fact that Aß deposition is not sufficient to cause cognitive decline in AD. Moreover, the rate of Aß accumulation is not related to neurodegeneration at baseline and only 8% of controls display both decreased hippocampal volume and increased PiB signal. According to Jack’s model, all of the aforementioned markers become positive well before dementia onset, and the ones related to amyloid pathology already reach their plateau at the time of first cognitive deficits. More recently, selective tau tracers became available for clinical research. Although a PiB equivalent is not yet ready for tau imaging, the recent development of tau tracers with higher selectivity, reduced non-specific binding and improved tracer kinetics compared to the first molecules raise increasing expectations among the scientific community. Given the tight association between tau deposition, cognition and neurodegeneration, and unlike Aß imaging, tau imaging will be essential for assessing disease progression. Furthermore, they may help to resolve the controversy about the temporal sequence of tau pathology in AD. The new diagnostic criteria by Dubois and collaborators consider that the development of tau pathology, at least under its fibrillar forms, is a late phenomenon in AD dependent, at least partly, on the Aß deposition in prodromal states. Recent contributions showed that tau-related markers (but also structural MRI changes) might become positive in the absence of PiB deposits mainly in preclinical cases. Ultimately, tau imaging will provide the tool to change the landscape and explore whether or not presymptomatic administration of anti-Aß therapy impacts on the progression of tau pathology that determines the clinical expression of AD.
Ann Marie Gillie works as an Education Assistant for Parkland County School Division in Alberta, Canada, where her role is working primarily with students who suffer from ADHD/ADD/ ODD and other behavior disorders. She was asked in 2012 to be a Canadian Advocate for Epilepsy and with her passion and drive for motivating others her role has taken her internationally to speak. She is also a published author (If Walls Could Talk and Let's Talk about Epilepsy) and had several articles published in regards to experience with epilepsy and surgery. Her topics of discussion at conferences and seminars are - her surgery (Left Selective Amygdalahippocampectomy), women and epilepsy, sex & seizures and her books. She is passionate about helping others that struggle with the disorder and her goal is to help others internationally.
Being diagnosed with Epilepsy at the age of 2 1/2 years old defiantly created several obstacles for myself and my family, but being the stubborn and positive individual that I am, I was able to get through it; I actually Beat Epilepsy. On December 03, 2002 my life was changed forever, I underwent neuro surgery at University of Alberta Hospital in Edmonton, Alberta, Canada. My surgery was called Left Selective Amygdala hippocampectomy and the procedure was a 100% success. I had 6 grand mal seizures two days before my surgery and those were my last, I can even say that I have been off all medications now for over 10 years. That is an extremely proud feeling. My past history with epilepsy was like a roller coaster, on meds, off meds, side effects, seizures, no seizures; it was a never ending hurtles, but I stayed strong and survived it. I was never in special needs classes; I played sports and was an individual with an infectious personality, so I am regularly told. Since my surgery in 2002, I have accomplished some amazing tasks and ones I would never have thought possible. I have published two books have had several articles published in papers and magazines, as well as international medical sites like SNI (Surgical Neurology International) and CURE. My number one goal is to educate others around the world, but not from a professional side of things but from someone that has lived it, that understands the obstacles others go through. From my understanding, there are not a lot of individuals that speak on the topic of epilepsy, locally or internationally and I want to change that. I have been a people person my whole life and I feel that there was a reason I am here today speaking about my story; Epilepsy needs to be talked about and I am the one to do that! I want to be that Voice for Epilepsy.
Texila American University, Guyana
Title: Charting the neural pathways on a dissected human brain to elucidate the commonality of abnormal networks in schizophrenia and bipolar disorder
Time : 14:00-14:25
Sanjoy Sanyal is Associate Dean, Clinical Neuroscience Professor, Surgeon and Informatician in Texila American University, Guyana, South America. He holds double Master's degrees from India and UK. He has published more than 50 papers in print and online journals. He is a Neuroscience editor and peer-reviewer of WebmedCentral. He has posted more than 300 Neuroscience videos online, accompanied by his running commentaries. He is currently writing a Neuroscience book for medical students. He has presented papers in more than 10 international forums. He holds a provisional patent from USPTO on a computerized program for staging 26 human cancers
While the pathophysiology of schizophrenia and bipolar disorders are poorly understood, researchers have used functional brain imaging in healthy volunteers and individuals with schizophrenia and BPD to map interrelationships between five brain networks. Brain networks are regions that function together and are responsible for its higher activities. Two networks showed diminished interactions in schizophrenia and BPD. On this platform of existing knowledge it was decided to chart the neural pathways on a dissected human brain and relate this to the pathophysiology of schizophrenia and BPD.
After sagittally dividing a formalinized human brain, five components of basal forebrain, ventral tegmental area and cingulate gyrus were located on the model. Next, the meso-cortical and meso-limbic pathways were charted out on the brain model. Then the most probable locations of pathology in Types-I and II schizophrenia were pinpointed in these pathways.
While obviously speculative, this approach enhances understanding of schizophrenia and BPD in several ways. Networks that are out of balance in both illnesses may be related to certain psychotic symptoms seen in both, such as delusions. This model provides the location of antipsychotic intervention on Dopamine-2 and 5HT-2 receptors for the amelioration of schizophrenia and possibly BPD symptoms. It also enables the neurologist to envisage the pathophysiology of schizophrenia and BPD in a more tangible way. Preliminary feedback from viewers of this model has been very positive. Finally, this brain model paves the way for focused imaging studies for more accurate localization of the pathological brain networks in both conditions
Johns Hopkins University, USA
Title: Cognitive effects of deep brain stimulation for essential tremor: evaluation at 1 and 6 years.
Time : 14:25-14:50
Martin Kronenbuerger, MD obtained his medical school training in Heidelberg, Germany and Lexington, Kentucky. He completed Neurology Residency at Aachen University Hospital, Germany, where he was subsequently attending Neurologist. He is currently a fellow in Movement Disorders at Johns Hopkins Hospital. He has published more than 25 papers in peer-review journals, most of them on Movement Disorders.
Essential tremor (ET) is a very prevalent tremor disorder. Tremor in ET is due to an over activity of cerebello-thalamic-cortical tracts. Newer evidence point to the existence of non-motor symptoms in ET such as neuropsychological deficits, related to a disturbance of the cerebello-thalamic/cortical tracts. There are no formal studies on the effects of drug treatment on neuropsychological performance in ET, and little is known about Deep Brain Stimulation (DBS) on neuropsychological deficits in ET. We systematically assessed the effects of DBS on neuropsychological functioning in ET patients. We examined nine ET patients before surgery (PRE-SURGERY), and 1 and 6 years thereafter with DBS switched on (DBS-ON) and off (DBS-OFF). Standardized neuropsychological tests and reaction time tests were applied. There were no differences in tasks of verbal fluency, memory, and executive and intellectual functions comparing PRE-SURGERY, DBS-ON, and DBS-OFF at 1 and 6 years post-surgery. Lesions caused by DBS electrode implantation led to an increase in simple reaction time, while the actual electrical stimulation restored impaired reaction time. Neither stereotactic surgery nor electrical stimulation affected higher cognitive processes in patients with ET in the short or long term. This study proposes that cerebello- thalamo-cortical pathways in humans are involved in tasks of simple reaction time.
University of Massachusetts School of Medicine, USA
Time : 14:50-15:15
Mehdi Ghasemi completed his M.D. in Tehran University of Medical Sciences (TUMS) in 2008. After working as a clinical researcher in Dept. of Psychiatry and senior researcher in Dept. of Pharmacology in TUMS, he joined Department of Neurology at Johns Hopkins University School of Medicine in 2009 as post-dctoral researcher. He was also the director of Neuroscience Clinical Research Program at Neurology Institute for Brain Health and Fitness (2012-2014). Ghasemi is currently a resident of neurology at University of Massachusetts Medical School. He has published over 80 papers/abstracts in peer reviewed journals and scientific conferences worldwide and serving as an editorial board member and ad hoc reviewer of many scientific international journals.
There is no doubt that the elderly population is growing worldwide and in the USA. As age advances, the likelihood of sleep disturbances increases, which leads to alterations in the quality and quantity of sleep. Complaints about sleep disturbances have been reported in approximately 50% of seniors more than 65 years old living at home and 65% of those residing in nursing home facilities. Persistent sleep disorders in these group of people are associated with impaired cognition, diminished intellect, poor memory, confusion, and psychomotor retardation all of which may be misinterpreted as dementia. Therefore, understanding of sleep disturbances and the efficient therapeutic approach to these disorders plays a key role in decreasing the likelihood of cognitive impairment in elderly and those patients with demetia. In this talk, we review the sleep pattern changes related to aging, and recent pathophysiologic theories underlying sleep diturbances (such as glymphatic system theory) and related cognitive impairment in patients with neurodegenerative disorders (such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia). We also discuss the most common sleep disorders related to the neurodegenerative disorders and therapeutic approaches to these disoroders.
- Session on: Pathophysiology | Analysis, Assesment and Diagnosis
Jina Pharmaceuticals, Inc., USA
National Taiwan University Hospital, Taiwan
Title: The temporal profiles of changes in nerve excitability indices in familial Amyloid Polyneuropathy
Time : 15:15-15:40
Ming-Jen Lee has completed his Neurology resident training at the age of 31 years from National Taiwan University Hospital (NTUH), Taipei, Taiwan. He completed his PhD course from Institute of Neurology, University College London, UK. He is an associate professor in the Department of Neurology, NTUH. He is in charge of the neurogenetic clinic for ten more years and is interested in the disease mechanism of peripheral neuropathy and neurocutaneous disorders. He has published more than 20 papers in reputed journals.
Familial amyloid polyneuropathy (FAP) is a rare genetic disorder frequently caused by a mutation in transthyretin (TTR) gene. There are two cardinal clinical features of TTR-FAP, autonomic dysfunction and sensorimotor polyneuropathy. To elucidate pathophysiological mechanisms of FAP, we evaluated the changes of the electrophysiological parameters in both patients (TTR, p.A97S mutation) and mutant carriers. The clinical phenotypes, neuropathy severity scores (NDS and ONLS), and the indices from nerve excitability test (NET) were collected. The median NDS and ONLS scores for patients are 54.5 (range, 13-82) and 4.5 (3-9), respectively. The nerve conduction studies showed markedly reduced CMAP and SNAP in patients, but unremarkable in carriers. NET data obtained from ulnar nerves of carriers showed increase of threshold, rheobase, and refractories in recovery cycle (RC). In the patient group, the NET study showed prolonged latency, reduced threshold elevation during hyperpolarizing threshold electrotonus (TE) at 10~40 ms (TEh(10-20ms) and TEh(20-40ms)), and increased refractoriness in the motor axons. There were prolonged latency, increased threshold reduction and S2 accommodation in depolarizing TE, lowed TEh(slope 101-140 ms), delayed time to overshoot after hyperpolarization, increased refractoriness and superexcitability in RC in sensory axons. The regression models demonstrated that the increase of refractoriness and prolonged relatively refractory period are correlated to the disease progression from carrier to patients. A defect in sodium current might be an early pre-symptomatic pathophysiological change considering the marked increase of refractoriness at short-width stimulus. Furthermore, the shallower slope of recovery, delayed time to overshoot after hyperpolarizing TE, and increase of superexcitability suggest a focal disruption of basal lamina and myelin membrane leading to the increase of intermodal capacity.
Nippon Medical School, Japan
Title: Comparison of frontal function during verbal fluency task by near-infrared spectroscopy and functional MRI
Time : 15:40-16:05
Michihiko Koeda is a senior assistant professor of the psychiatry department at Nippon Medical School, Tokyo, Japan. He completed his PhD at the Medical Research Institute of Tokyo Medical and Dental University. He was a visiting researcher at the University of Glasgow. He is continuing to investigate auditory brain function by the use of functional MRI to clarify the pathophysiology of psychiatric symptoms, and pharmacological and/or genetic effects.
In order to understand the pathophysiology of depression, development of a convenient clinical application for evaluating frontotemporal function using near-infrared spectroscopy (NIRS) is a very important challenge. In terms of time resolution, NIRS is more effective than functional MRI (fMRI), although anatomical resolution is not much better than by fMRI. However, whether the significant brain activation by NIRS is equivalent to that shown by fMRI is unclear. To confirm the anatomical validity of brain function, in the present study, by comparing the results of NIRS and fMRI, we investigated frontotemporal function during verbal fluency. 20 normal subjects participated in this study. Brain function of all subjects was examined by both NIRS and fMRI during a verbal fluency procedure. Two tasks were examined; period A: they simply spoke vowel sounds repeatedly; period B: they spoke words as much as possible after their initials were displayed. In both the results of NIRS and fMRI, under the condition of period B compared with period A, a significant activation was observed in the bilateral dorsolateral prefrontal gyrus. From these findings, we concluded that frontal activation of verbal fluency by NIRS conveniently reflects frontal brain function by fMRI.
Geisel School of Medicine at Dartmouth, USA
Title: High-resolution diffusion tensor spinal cord MRI measures as biomarkers of disability progression in a rodent model of progressive multiple sclerosis
Time : 16:05-16:30
Francesca Gilli, received her MS in Medical Biotechnology and PhD in Human Biology from the University of Torino (Italy). She then completed her postdoctoral research in neuroimmunology at University of Torino (Italy), University of Basel (Switzerland), and Geisel School of Medicine at Dartmouth (USA). She currently serves as Assistant Professor of Neurology at Geisel School of Medicine at Dartmouth, where she works as a basic scientist. Her research focuses on attempting to understand the basic biology of neuroinflammation, demyelination and neuronal injury in Multiple Sclerosis. She has published more than 37 papers in peer-reviewed journals including 23 as main author.
Standard MRI sequences have been shown to be insensitive and non-specific in monitoring multiple sclerosis (MS) disease progression. This lack of reliability of spinal cord imaging in identifying significant disease is a major problem in the clinical management of MS patients. In the present study, we sought to address this gap by testing the hypothesis that diffusion tensor imaging (DTI), an advanced imaging technique, can reliably quantitate MS disease in the spinal cord, by using a well-characterized animal model of progressive MS, i.e. Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD).
SJL mice with TMEV-IDD and varying levels of clinical disease were imaged using a 9.4T horizontal bore small animal MRI scanner. Axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were calculated. These DTI metrics were obtained for several regions-of-interest (ROIs) in the spinal cord, namely dorsal, dorsal-lateral, ventral and ventral-lateral white matter (WM) and gray matter (GM). Progressive disability in mice was assessed by the Rotarod performance test and disability data were expressed as a neurological function index (NFI). Correlation was then performed between DTI metrics and disability scores. TMEV-IDD mice displayed significant increased neurological deficits over time when compared with sham mice (two-way ANOVA p<0.0001). Concurrently, the values of FA and AD were both significantly decreased compared to sham controls (both p<0.0001), while RD was increased (p<0.0001). Overall, FA changes were greater in WM than in GM, and differences were more pronounced in the ventral region. Interestingly, lower NFI scores were associated with decreased FA values measured in the ventral (r=0.68; p<0.0001) and ventral-lateral (r=0.70; p<0.0001) regions of the WM, but not in the dorsal region of the WM (r=0.08; p=0.625) and the GM (r=0.24; p=0.170).
In conclusion, these data demonstrate that improved DTI measures of the spinal cord contribute to strengthening the association between neuroradiological markers and clinical disability, and support the routine use of DTI measures in spinal cord imaging in MS patients.
University hospital Dubrava, Croatia
Title: SEEG in preoperative assessment and treatment of patients with refractory epilepsy – Croatian experience
Time : 16:50-17:15
Silvio Basic earned his medical degree at the Zagreb University Medical School in 1995 and obtained PhD degree in 2006. He works at the University hospital Dubrava in Zagreb as the Deputy Director, Head of the Department of Neurology and as the Head of the Referral Centre of Croatian Ministry of Health for Preoperative Assessment of Patients with Pharmacoresistant Epilepsy.
His primary field of interest is epilepsy management, especially management of patients with drug-resistant epilepsy using minimally invasive digagnostic and surgical procedures. He is the author of many scientific papers and articles with more than 150 citations
Stereoelectroencephalograpy (SEEG) is methodology in preoperative invasive monitoring of drug-resistant epilepsy patients with almost 60 years of clinical use. It is an established technique in Europe, especially in France in Italy, and it has been rapidly accepted as favourable preoperative method in huge number of epilepsy centres around the world, including USA and Canada. It enables tailored individualized surgical excision based on precise localization of the epileptogenic zones, especially those localized in deep cortical structures. Its main advantage is precise epileptogenic zone detection with minimally invasive approach, especially in cases when bilateral explorations are needed. Additional advantage of this technique is a possibility of intervention by using temporarily implanted depth electrodes. SEEG guided radiofrequency thermocoagulation is a treatment option for patients with drug-resistant focal epilepsy. By using implanted depth electrodes for invasive monitoring and epileptogenic zone detection, it is, at the same time, possible to perform thermolesions of the epileptic foci avoiding craniotomy and standard neurosurgical procedures.
Croatian experience with SEEG in preoperative assessment and as a treatment option in patients with drug-resistant epilepsy will be presented.
Amir Mufaddel has graduated from Khartoum University and did his MD in Psychiatry from Sudan Medical Specialization Board in 2008. Currently he is working in
Al Ain Hospital, Community Mental Health Services. He is also an Adjunct Lecturer in United Arab Emirates University. He has published several papers in reputed
journals mostly refl ecting the psychiatric aspects of physical conditions such as neurology, infectious diseases and dermatology
Psychiatric symptoms can be associated with several systemic and central nervous system infections and they can be the initial presenting symptoms, occurring in the absence of neurological symptoms in some disorders as in some cases of viral encephalitis. They could also be part of the clinical picture in other cases such as psychosis or mood symptoms secondary to brucellosis or toxoplasmosis. Late-onset neuropsychiatric complications may also occur several years following the infection such as in the case of subacute sclerosing panencephalitis due to measles. Some Infectious diseases may have possible etiological role for major psychiatric disorders, based on yet unconfirmed reports for viral infectious diseases (e.g. Influenza virus and HSV-1) which are thought to have risk for developing schizophrenia and psychosis. Neuropsychiatric adverse effects can occur due to drugs (e.g. mefloquine, interferon-alpha) that are used for treatment of infectious diseases. Psychiatric symptoms can also be reactivated resulting from chronic, complicated and serious infections such as HIV that can lead to depression, anxiety or adjustment disorders, although CNS involvement can also be a possible etiological factor. Patients suffering from primary and severe psychiatric disorders are at increased risk of contracting infection; that is mainly related to high risk behaviors in patients with mania or schizophrenia. It is also important to consider that the co-occurrence of psychiatric symptoms and infection can be incidental (i.e. infectious diseases can occur in psychiatric patients regardless of the above mentioned factors). Early identification of the underlying etiology for organic/secondary psychiatric symptoms is essential for appropriate intervention and early treatment of the primary condition that could be the etiology of psychiatric symptoms so as to avoid unnecessary long-term psychiatric treatment and to avoid complications of possible misdiagnosis or delayed diagnosis of the primary condition.
- Session on: Structural and Functional Brain | Addiction & Brain Disorders
Texila American University, Guyana
Holy Name Hospital, New Jersey
Lehrer received his M.D. degree from the State University of New York in 1956. He completed his Post Graduate education in the Specialty of Otolaryngology and Head and Neck Surgery at Mount Sinai Hospital in NYC, became Board Certified, and was on the Attending Staff and taught at the Hospital for 10 years before moving his practice to New Jersey. He has specialized in Neurotology, and is a Member of the American Neurotology Society, as well as other Societies in that specialty. His papers and letters to the Editor concerning Vestibular and Auditory Disorders have been published in major specialty and general journals. He has presented at National and International meetings on Inner Ear disorders and has served on the Faculty of Meetings devoted to Inner Ear disorders. His major focus at this point in his career has been on Vestibular disorders with regard to Diagnosis and Management of these disorders and their effects upon Brain Function
The Vestibular System is ancient contributor to Central Nervous System function, historically over 500 million years old. It has evolved to become more complex in Vertebrates. It provides precise information with respect to Gravity and Head movements which allows vertebrates to maintain balance and spatial orientation. In Humans, as in most Vertebrates, it provides such information to the Brain in concert with the Visual and Proprioceptive Systems with some contribution from the sense of Touch.
Distortions, or loss, of vestibular inputs have been known, for centuries, to adversely affect balance. However, only recently, for decades, has knowledge surfaced indicating other effects on Brain function, particularly with regard to accompanying dysfunctions of the Visual, Cognitive and Affective Systems.
The aim of the Presentation is to describe these adverse effects of Vestibular dysfunction as seen in a Neurotologic practice, and to provide literature describing these issues. The Presenter has concluded, rom his observations of patients, and his review of the literature that the Vestibular System provides information basic to Brain functions other than balance and spatial orientation. He hopes to inform and stimulate the Audience to consider the diffuse role of the Vestibular System in Brain function.
Osvaldo Francisco Ribas Lobos Fernandez Graduated in Social Sciences from the Universidade Estadual Paulista Julio de Mesquita Filho (1987 ) , master's degree in Social Sciences from the Catholic University of São Paulo ( 1993) and a PhD in Social Sciences from the Federal University of Bahia (2007 ) . He was visiting professor and conducted post-doctoral research in urban anthropology at Columbia University in New York City. He was visiting professor at the School of Public Health, University of São Paulo, performing in stage sabbatical stage . He is currently full professor of anthropology in the course of social sciences , education department , the Bahia State University . It has experience in the field of the Anthropology, with an emphasis on medical and urban anthropological theories, researching the following subjects: consumption of illegal drugs , homosexuality, violence , homophobia, schools and training teachers and health professionals
This article presents results of a long fieldwork that included direct observation of four cocaine user groups, application of two series of interviews and detailed tracking of eleven subjects in the Greater São Paulo. The consumers were predominantly characterized as being regular users, includes some casual users, but with a long history of cocaine use by the inhaled route. The survey was conducted in two periods, 1994 and 2006. After 12 years, users were re-interviews conducted and contact re-established with some users, enabling the visualization of different trajectories and career developed over time, indicating different patterns substance use.
As the main methodological strategy, participant observation was adopted, in order to better understand the groups and select the respondents. Depending on the degree of acceptance shown by different subjects, you could have privileged access to information normally hidden and get so a partial view of trade and drug trafficking network. Such observations were crucial to collect data on consumption, social rituals and performances of users, comparing views and information given by key informants in interviews with direct observations collected by the researcher. Thus, the ethnographic research focused on the scenes and patterns of use of various networks of sociability of different territories and lifestyles.
Some users were observed and classified as key informants of the observed users were selected as key informants, giving preference to those who proved willing to maintain a continuous dialogue with the researcher in the field, as well as having a good insertion in different territories and networks of consumers of coca-based products. On being interviewed, they were able to describe their own consumption, other consumer profiles, the sociocultural context, lifestyles, worldviews and social imaginary around consumption.
Our intention was to contextualize different forms of cocaine use, relating them to the lifestyles in the metropolis and the sociability of individuals in the urban middle classes. Therefore, we focus on the description of the ethnographic process, the selection of respondents (key informants), the characterization of the case studies and the changes in the market and experienced by consumers, etc.
The research is concentrated in São Paulo, where they were subject to several scenes of use, or scenarios. These, however varied they were, were characterized by discretion and / or privacy. They included, among them, bars, clubs, classrooms, home parties and villas, located in different areas of the city (Central, West, North and East). The study was the use of cocaine inhaler, trying to understand the culture and consumption rituals developed around the substance and their different usage patterns. More specifically, interested us the informal rules and controls developed by users on self-regulation of consumption.
In this research, our respondents reported periods of cocaine use that ranged from a minimum of seven to a maximum of thirty-five years. To analyze and interpret the data collected, we separated the group of users who had developed problems arising from their use of cocaine and other drugs from those who had not developed “problematic” use patterns taking into account the consequences in terms of their impact on the subjects´ physical and mental health, and in terms of possible social consequences (imprisonment, psychiatric hospitalizations and others).The research focused on the construction of cocaine use styles, and drew on suggestions made by Zinberg (1984) about "compulsive" and "controlled" drug use. Following the ethnographic evidence for the particular meanings attributed to cocaine use in each different lifestyle (Bieleman & BIE, 1992;. DIAS, et al, 1992; Grund, 1993), the label of light users and hard, native terms, currents in time among our middle-class subjects in São Paulo.
We considered to be light users, those who had not developed health problems stemming from cocaine use and who were not engaged in crime. This type of user does not miss work, develops strategies to deal efficiently with everyday life, is involved in networks of social relations, employs a series of rituals and product usage rules, deals with his cocaine differently from the compulsive and / or dysfunctional user and makes a series of efforts to maintain the stability of his use. We reviewed their drug using careers, focusing our interest on their development of informal controls, their understanding of changes that might occur in their usage patterns and the relationship between use and abuse in certain moments of their lives, trying to unravel the various social processes that contribute to shape their practices and the varied meanings attributed to them. We believe that they are equivalent to the "controlled user" discussed by Zinberg.
We classified as hard or compulsive users those who presented physical or social consequences of their drug use and who have to resort more frequently to expert help than the so-called light users. The hard users do not usually restrict themselves to using inhaled cocaine, and generally admit to the other forms of cocaine use or to the consumption of other substances, like marijuana.
Kazakh National Medical University, Kazakhstan
Saule T.Turuspekova MD, PhD, neurologist highest category, Professor of the Department of internship and residency in neurology of KazNMU. 1995- PhD Thesis -"Vegetative-vascular disorders in cerebral manifestations of diabetes mellitus." 2010 - Doctoral thesis - "The influence of small doses of ionizing radiation on the nervous system". Over 100 scientific papers which were presented at international conferences in many countries. State scholarship for talented young scientists of the Ministry of Science of the Republic of Kazakhstan. Coordinator of the Russian Youth Academy of Sciences (Samara). 2015-the personal physician of the Kazakhstan astronaut Aydin Aimbetov. Member of the ESO, WSO, «Neurosciences», EAN.
It is known that alcohol remains the predominant form of addictive diseases worldwide. Alcohol use is a major risk factor for mortality in men aged 15-59 years.The basis of alcoholic nervous system disorders are neyrometabolizm, the development of which is related to pathogenic factors: nutritional, glutamatergic factor (excitotoxic effects of glutamate), GABAergic factor (reduction of GABA in nerve tissue).The highest value in the alimentary pathogenic mechanism is deficiency of thiamine (vitamin B1).
Objective: To evaluate the efficacy of benfotiamine for the correction of cognitive functions in patients with chronic alcoholism.
Material and Methods: Observed 68 patients with chronic alcoholism lasting no more than 10 years aged 25-50 years. To determine the degree of cognitive impairment used Mini-Mental State Examination (MMSE), a brief scale of the Montreal Cognitive Assessment (MoCA), Mini-Cog test, proofreading test Bourdon, test for mirroring, test for reciprocal coordination. Under supervision there were 2 groups: 1st - 53 patients who received 300 mg benfotiamine; 2 rd-15 control patients treated according to the protocol.
Results: more than 83% of patients with chronic alcoholism identified cognitive impairment. According to MoCA average value was 20,8 points. There was a significant positive dynamics of cognitive functions according to the MoCA test in the intervention group (from 20,8 to 24,6 points) compared with controls (20,8- 21,3 ). Also, there was an improvement in terms of proofreading Bourdon samples and other tests.
Conclusions: Thus, the dynamics of the research shows the positive effect of receiving benfotiamine on cognitive function in patients with chronic alcoholism.